A quantitative model of transcription regulation reveals the role of non-conserved enhancers

We identify sites of combinatorial control by performing high throughput ChIP experiments on p300, CREB-binding protein (CBP), the deacetylase SIRT1 and on multiple DNA-binding transcription factors in three different tissues. We present a quantitative model of transcriptional regulation that reveals the contribution of each binding site to tissue-specific gene expression in several mouse cell types. Binding to both evolutionarily conserved and non-conserved sequences is found to contribute significantly to transcriptional regulation. We demonstrate that binding location strongly predicts the expression level of nearby genes. Overall design: Liver hepatocytes and cerebellum tissue were harvested from male C57BL/6J mice. RNA was extracted and hybridized to Affymetrix arrays. Examination of transcriptional regulator binding in three mouse tissues by ChIP-IP using tiling arrays. Examination of CBP binding in mouse liver and cerebellum by ChIP-seq.